Factors associated with the response of the cell to herpes simplex virus infection

Summary Four factors were shown to participate in the outcome of herpes simplex infection in tissue cultures: (a) the innate susceptibility of the cell (b) temperature (c) antibody and (d) interferon. Antibody appeared to function only to localize infection in KB cells (it failed to protect rabbit kidney cells) when added to the cultures following adsorption of virus. The critical factor in long-term protection of cells was a substance with several properties of interferon. The substance was produced when the entire infectious process was allowed to proceed at 35° C but was not produced under conditions where infected cells were first maintained at 25° C and later shifted to 35° C. Under the latter conditions antibody failed to restrain the progress of cellular destruction. Death of the total population occurred whenever interferon was not produced or was deliberately removed. Survival of the majority of cells was possible in the absence of antibody only as long as interferon was present in the culture. Certain findings also imply that although at 25° C there was neither virus multiplication nor interferon production, an early event(g) leading to the former and apparently blocking the latter takes place at this suboptimal temperature.This investigation was supported by Public Health Service Training Grant No. CA 5075 from the National Cancer Institute, Public Health Service General Research Support Grant No. FR 5516 and Office of Naval Research Contract No. 3310(00).     

Severe, late-onset graft-versus-host disease in a liver transplant recipient documented by chimerism analysis

A 52-year-old liver transplant recipient presented 8 months after transplantation with oral thrush, then 3 days later with oral ulcers and a diffuse rash, and 5 days later with an acutely reduced white blood cell count, rash, fever, and diarrhea. Bone marrow biopsy revealed severe aplasia. Although graft-versus-host disease (GVHD) was considered, the late onset of these symptoms was felt to render this etiology unlikely because GVHD usually occurs 2 to 6 weeks after transplantation. All potentially myelosuppressive medications were discontinued, and the patient was treated with high doses of hematopoietic growth factors. Because his symptoms continued, chimerism analysis was performed, which indicated that 96% of the peripheral blood mononuclear cells were of liver-donor origin. Ultimately, the patient underwent an allogeneic peripheral blood hematopoietic progenitor cell transplant from a human leukocyte antigen-identical brother, but he died 5 days after transplantation of overwhelming Candida kruseii infection. To our knowledge, this is the first chimerism-analysis-documented case of severe acute GVHD presenting so late after liver transplantation. It is of note that the patient had no known risks for GVHD in that he was relatively young and shared only one major human leukocyte antigen with his donor. Consideration should be given to GVHD as a cause of bone marrow aplasia at any time after organ transplantation. Storage of cell pellets from all transplant recipients and donors is highly recommended to facilitate the diagnostic evaluation.     

Radiology information systems,picture archiving and communication systems,teleradiology— Overview and design criteria

Information technology (IT), long taken for granted in commercial settings, is now being utilized for healthcare applications. Medical imaging has lagged comparatively due to the extremely vast data content of each frame; thus, the requirement for expensive high-end components. Further, IT in radiology has evolved from two distinctly separate camps—information systems, known as RIS (radiology information systems) and PACS (picture archiving and communications systems). Both RIS and PACS applications have migrated to the PC environment, enabling cost-effective implementation, but from two backgrounds: RIS from vendors using conventional information systems platforms and products, and PACS from radiographic film and modality vendors. The radiology department at Texas Tech University has assembled a seamlessly integrated, enterprise-wide RIS/PACS/teleradiology intranet. The design criteria include user-friendliness, flexibility to respond to changing needs, and open modular architecture to assure interoperability, cost-effectiveness, and future-proofing of investment. Since no single venor could provide an integrated system meeting our specifications, we decided to assume the burden of constructing our own system. As the system integrator, we embrace open architecture, thus enabling the incorporation of industry-standard-compliant, COTS (commercially off the shelf) products as modules. Microsoft Windows NT operating system, Visual C++ programming language, TCP/IP (transmission control protocol/internetworking protocol), relational SQL (structured query language) database, ODBC (open database connectivity), HL-7 (health level seven) and DICOM (digital imaging and communications in medicine) interfaces are utilized. The usage of COTS components reduces the cost to very affordable levels. With this approach, any module in our system can be replaced when outmoded, without affecting other modules in our system, making it truly future-proof. Construction and evolution of our system (TECHRAD) is reviewed.     

Autoimmune associated recurrent abortions

A possible relationship between recurrent spontaneous abortionsand autoimmune abnormalities was studied. Eight serologicalautoimmune or autoimmune-correlated parameters were investigatedin 91 women with unexplained recurrent abortions (3 consecutive,spontaneous abortions) and 89 fertile control women. Five parameterswere seen significantly more frequently in 19 women with atleast one second trimester miscarriage which had been associatedwith severe intrauterine growth regardation (IUGR), than incontrols. Seventeen of these 19 patients (89%) had at leastone positive autoimmune parameter, compared to 15 of 72 patients(21%) with no second trimester abortions with IUGR (P < 0.0001)and 14 (16%) of the controls (P < 0.0001). No single autoantibodycharacterized patients who exhibited a significant accumulationof autoimmune parameters. These findings may suggest that womenwith recurrent abortions, in whom autoimmunity is thought toplay a role, cannot be identified merely by one laboratory assay,such as that for cardiolipin antibodies, but must be definedby positivity of several criteria. Using our own test panel,preliminary clinical and serological criteria have been setup for the definition of an autoimmune-associated recurrentabortion condition. Twenty-three per cent of the patients inour material fulfilled these criteria, and seven out of nineof these women (78%) have to date been treated successfullywith heparin/aspirin during pregnancy.     

Joint Photographic Experts Group (JPEG) compatible data compression of mammograms

We have developed a Joint Photographic Experts Group (JPEG) compatible image compression scheme tailored to the compression of digitized mammographic images. This includes a preprocessing step that segments the tissue area from the background, replaces the background pixels with a constant value, and applies a noise-removal filter to the tissue area. The process was tested by performing a just-noticeable difference (JND) study to determine the relationship between compression ratio and a reader's ability to discriminate between compressed and noncompressed versions of digitized mammograms. We found that at compression ratios of 15∶1 and below, image-processing experts are unable to detect a difference, whereas at ratios of 60∶1 and above they can identify the compressed image nearly 100% of the time. The performance of less specialized viewers was significantly lower because these viewers seemed to have difficulty in differentiating between artifact and real information at the lower and middle compression ratios. This preliminary study suggests that digitized mammograms are very amenable to compression by techniques compatible with the JPEG standard. However, this study was not designed to address the efficacy of image compression process for mammography, but is a necessary first step in optimizing the compression in anticipation of more elaborate reader performance (ROC) studies.     

Anomalous biological effects of salicylates and prostaglandins

While some salicylates (salicyclic acid and salicylaldehyde, especially) are as potent as aspirin as acute, orally-active anti-inflammatory drugs in the rat, they are either inactive or far less potent as PG synthesis inhibitors when added directly to isolated platelets or when given orally.Although PGE₁ and PGE₂ produce anti-ulcerogenic effects when given to rats in the presence of selected nonsteroidal anti-inflammatory drugs, they fail to inhibit the acute anti-inflammatory and anti-nociceptive effects of these drugs. They are anti-inflammatory and anti-nociceptive under certain experimental conditions. PGE₁ and PGE₂ can also behave as hypothermic agents when given subcutaneously. Related studies, using PG synthesis stimulators in vivo and in vitro (substituted phenylureas), also cause anti-nociception and hypothermia.All of these indirect studies, when taken together, infer that PG synthesis inhibitionper se fails to explain, entirely, the pharmacologic effects of non-steroidal anti-inflammatory drugs. They also suggest that the precise role of certain PGs in toxicopharmacology is far from simple and straightforward.     

Comparative analysis of multilocus sequence typing and pulsed-field gel electrophoresis for characterizing Listeria monocytogenes strains isolated from environmental and clinical sources

One hundred seventy-five Listeria monocytogenes strains were characterized by serotyping, pulsed-field gel electrophoresis (PFGE), and multilocus sequence typing (MLST) based on loci in actA, betL, hlyA, gyrB, pgm, and recA. One hundred twenty-two sequence types (STs) were identified by MLST based on allelic profiles of the four housekeeping genes (betL, gyrB, pgm, and recA), and 34 and 38 alleles were identified for hlyA and actA, respectively. Several actA and hlyA alleles appeared to be predominantly associated with clinical isolates. MLST differentiated most of the L. monocytogenes strains better than did PFGE, and the discriminating ability of PFGE was better than that of serotyping. Several strains with different serotypes were found, by MLST and PFGE, to have very closely related genetic backgrounds, which suggested possible "antigen switching" among them. MLST can be a useful typing tool for differentiating L. monocytogenes strains (including strains undistinguishable by PFGE typing and serotyping), and it may be of value during investigations of food-borne outbreaks of listeriosis.     

Effects of Bloom's syndrome fibroblasts on genetic recombination and mutagenesis of herpes simplex virus type 1

The effects of Bloom's syndrome (BS) fibroblasts on genetic recombination and the mutation frequency of herpes simplex virus type 1 (HSV-1) was determined by employing two factor crosses of selected temperature-sensitive (ts)mutants. A significant increase in the recombination frequency (RF) was observed in seven of nine crosses when multiple BS fibroblast lines were compared to normal human fibroblasts. The RF of HSV-1 ts mutants increased following 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment of normal, but not BS fibroblasts, suggesting that BS fibroblasts express higher constitutive levels of genetic recombination activity. HSV-1 ts mutants demonstrated significantly higher reversion frequencies to the nontemperature sensitive (ts⁺)phenotype following growth in BS rather than normal fibroblasts, indicating that exogenous viral DNA encoding many of the enzymes necessary for its own replication is affected by the mutator phenotype of BS.Presented in part at the American Association for Cancer Research, May 1986, Los Angeles, California.     

Evaluation of Gen-Probe amplified mycobacterium tuberculosis direct test by using respiratory and nonrespiratory specimens in a tertiary care center laboratory

The performance of the Amplified Mycobacterium Tuberculosis Direct (AMTD) test (Gen-Probe Inc., San Diego, Calif.) was assessed in a large tertiary care mycobacteriology laboratory. Both acid-fast smear-positive and smear-negative respiratory and nonrespiratory clinical specimens were analyzed. From February 1998 to 4 October 2001, AMTD assays were performed on 391 respiratory specimens and 164 nonrespiratory specimens. The AMTD assay was compared to the "gold standard" of combined culture and clinical diagnosis. The overall sensitivity for all specimens, including those for which no smear result was available, was 91.2%. The overall sensitivities of the assay, including acid-fast smear-positive and -negative specimens, were 97.8 and 77.3% for respiratory and nonrespiratory specimens, respectively. The corresponding specificities for respiratory and nonrespiratory specimens were 99.1 and 98.5%, respectively. The overall specificity for all specimens was 98.9%. Positive and negative predictive values were 93.9 and 99.7% and 91.7 and 96.4% for respiratory and nonrespiratory specimens, respectively. The time saved by using the AMTD test for making a diagnosis of tuberculosis instead of using culture was 8.99 days. Inhibitors to the AMTD assay were found in 3.1% of respiratory specimens and 3.1% of nonrespiratory specimens. The assay, used in a general mycobacteriology laboratory setting, represents an important advance in improving the speed and accuracy of diagnosis in the management of patients with tuberculosis.